: Infection with gram- negative bacteria following multiple injury or burn is a common occurrence and often leads to multiorgan failure. Effective therapy in this patient group is lacking and, consequently, mortality rates are unacceptably high. An array of symptoms is observed clinically, regardless of the type of infecting gram-negative organism. It is now well accepted that it is the endotoxin (PLS) of gram-negative bacteria that initiates host responses producing septic shock. Numerous studies provide support for the involvement of monocytes/macrophages (MO) and neutrophils (PMN) in the earliest responses to LPS. Central to these responses is LPS-induced release of cytokines from MO and increased oxidative metabolism of PMN. Great progress has been made in defining how these mediators contribute to cellular injury leading to septic shock. There is a significant gap in our knowledge about cellular receptors and second messenger pathways relaying signals from LPS. Recent advances have provided new insights into events at the plasma membrane surface that control LPS recognition. This includes the identification of CD14 as a plasma membrane receptor for protein (LBP). The net effects of the LBP/CD14 pathway are to markedly enhance cell sensitivity to LPS and to induce more rapid responses; i.e., cytokine release or cell priming. There is also new information about potential candidates for plasma membrane lipid A receptors that are independent of the LBP/CD14 pathway. How information is relayed from occupied receptors is less clear, although new information is being obtained about intracellular signalling pathways used by LPS. The results of this rapidly expanding body of data are new opportunities for therapeutic intervention in diseases where LPS plays a role. This will form the basis of the proposed Keystone meeting.